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Multiple diagnostic modalities are urgently needed to identify early-stage kidney diseases. Various molecules have been investigated; however, most studies have focused on identifying specific biomarkers in urine. Considering that assessing the symmetrical dimethylarginine (SDMA) plasma concentration is more suitable as an early diagnostic test for chronic kidney disease (CKD) in routine veterinary practice, we aimed to investigate the clinical usefulness of plasma neutrophil gelatinase-associated lipocalin (pNGAL) and plasma kidney injury molecule-1 (pKIM-1) concentrations for CKD detection in small-breed dogs. Through a retrospective analysis, we found that numerous clinicopathological data showed a log-normal distribution, even when they satisfied normality tests. Moreover, the log-transformed pNGAL and pKIM-1 concentrations successfully identified CKD International Renal Interest Society (IRIS) stages 1-4 and the risk group with underlying CKD risk factors. Correlation analysis and group comparison of other factors confirmed the possibility of using these two biomarkers for detecting the CKD risk group and IRIS stage 1. Receiver operating characteristic curve analysis revealed that the diagnostic accuracy for discriminating the risk group was superior in the order of pKIM-1, pNGAL, SDMA, and serum creatinine levels. In conclusion, these results suggest that pKIM-1 and pNGAL are possible early or quantifiable markers of insignificant CKD or can be at least used as an adjunct with traditional indicators.
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The conventional technique for successful bone grafts, involving the use of a patients own tissue (autografts), is challenged by limited availability and donor site morbidity. While allografts and xenografts offer alternatives, they come with the risk of rejection. This underscores the pressing need for tailor-made artificial bone graft materials. In this context, injectable hydrogels are emerging as a promising solution for bone regeneration, especially in complex maxillofacial reconstruction cases. These hydrogels can seamlessly adapt to irregular shapes and conservatively fill defects. Our study introduces a shear-thinning biomaterial by blending silicate nanoplatelets (SNs) enriched with human blood-derived plasma rich in growth factors (PRGF) for personalized applications. Notably, our investigations unveil that injectable hydrogel formulations comprising 7.5% PRGF yield sustained protein and growth factor release, affording precise control over critical growth factors essential for tissue regeneration. Moreover, our hydrogel exhibits exceptional biocompatibility in vitro and in vivo and demonstrates hemostatic properties. The hydrogel also presents a robust angiogenic potential and an inherent capacity to promote bone differentiation, proven through Alizarin Red staining, gene expression, and immunostaining assessments of bone-related biomarkers. Given these impressive attributes, our hydrogel stands out as a leading candidate for maxillofacial bone regeneration application. Beyond this, our findings hold immense potential in revolutionizing the field of regenerative medicine, offering an influential platform for crafting precise and effective therapeutic strategies.
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mRNA therapy is the intracellular delivery of messenger RNA (mRNA) to produce desired therapeutic proteins. Developing strategies for local mRNA delivery is still required where direct intra-articular injections are inappropriate for targeting a specific tissue. The mRNA delivery efficiency depends on protecting nucleic acids against nuclease-mediated degradation and safe site-specific intracellular delivery. Herein, we report novel mRNA-releasing matrices based on RGD-moiety-rich gelatin methacryloyl (GelMA) microporous annealed particle (MAP) scaffolds. GelMA concentration in aerogel-based microgels (µgels) produced through a microfluidic process, MAP stiffnesses, and microporosity are crucial parameters for cell adhesion, spreading, and proliferation. After being loaded with mRNA complexes, MAP scaffolds composed of 10 % GelMA µgels display excellent cell viability with increasing cell infiltration, adhesion, proliferation, and gene transfer. The intracellular delivery is achieved by the sustained release of mRNA complexes from MAP scaffolds and cell adhesion on mRNA-releasing scaffolds. These findings highlight that hybrid systems can achieve efficient protein expression by delivering mRNA complexes, making them promising mRNA-releasing biomaterials for tissue engineering.
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Responsive heat resistance (by heat shock protein upregulation) and spontaneous reactive oxygen species (ROS) detoxification have been regarded as the major obstacles for photothermal/photodynamic therapy of cancer. To overcome the thermal resistance and improve ROS susceptibility in breast cancer therapy, Au ion-crosslinked hydrogels including indocyanine green (ICG) and polyphenol are devised. Au ion has been introduced for gel crosslinking (by catechol-Au3+ coordination), cellular glutathione depletion, and O2 production from cellular H2O2. ICG can generate singlet oxygen from O2 (for photodynamic therapy) and induce hyperthermia (for photothermal therapy) under the near-infrared laser exposure. (-)-Epigallocatechin gallate downregulates heat shock protein to overcome heat resistance during hyperthermia and exerts multiple anticancer functions in spite of its ironical antioxidant features. Those molecules are concinnously engaged in the hydrogel structure to offer fast gel transformation, syringe injection, self-restoration, and rheological tuning for augmented photo/chemotherapy of cancer. Intratumoral injection of multifunctional hydrogel efficiently suppressed the growth of primary breast cancer and completely eliminated the residual tumor mass. Proposed hydrogel system can be applied to tumor size reduction prior to surgery of breast cancer and the complete remission after its surgery.
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Neoplasias de la Mama , Hipertermia Inducida , Fotoquimioterapia , Humanos , Femenino , Especies Reactivas de Oxígeno/metabolismo , Hidrogeles/uso terapéutico , Peróxido de Hidrógeno , Verde de Indocianina/uso terapéutico , Verde de Indocianina/química , Neoplasias de la Mama/tratamiento farmacológico , Proteínas de Choque TérmicoRESUMEN
This Roadmap on drug delivery aims to cover some of the most recent advances in the field of materials for drug delivery systems (DDSs) and emphasizes the role that multifunctional materials play in advancing the performance of modern DDSs in the context of the most current challenges presented. The Roadmap is comprised of multiple sections, each of which introduces the status of the field, the current and future challenges faced, and a perspective of the required advances necessary for biomaterial science to tackle these challenges. It is our hope that this collective vision will contribute to the initiation of conversation and collaboration across all areas of multifunctional materials for DDSs. We stress that this article is not meant to be a fully comprehensive review but rather an up-to-date snapshot of different areas of research, with a minimal number of references that focus upon the very latest research developments.
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As miniaturized and simplified stem cell-derived 3D organ-like structures, organoids are rapidly emerging as powerful tools for biomedical applications. With their potential for personalized therapeutic interventions and high-throughput drug screening, organoids have gained significant attention recently. In this review, we discuss the latest developments in engineering organoids and using materials engineering, biochemical modifications, and advanced manufacturing technologies to improve organoid culture and replicate vital anatomical structures and functions of human tissues. We then explore the diverse biomedical applications of organoids, including drug development and disease modeling, and highlight the tools and analytical techniques used to investigate organoids and their microenvironments. We also examine the latest clinical trials and patents related to organoids that show promise for future clinical translation. Finally, we discuss the challenges and future perspectives of using organoids to advance biomedical research and potentially transform personalized medicine.
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Investigación Biomédica , Organoides , Humanos , Células Madre , Medicina de Precisión/métodos , Investigación Biomédica/métodos , Desarrollo de MedicamentosRESUMEN
Indocyanine green (ICG), glucose oxidase (GOx), and copper(II) sulfate (Cu)-installed hybrid gel based on organic nanorod (cellulose nanocrystal [CNC]) and inorganic nanodisk (Laponite [LAP]) was developed to perform a combination of starvation therapy (ST), chemodynamic therapy (CDT), and photothermal therapy (PTT) for localized cancers. A hybrid CNC/LAP network with a nematic phase was designed to enable instant gelation, controlled viscoelasticity, syringe injectability, and longer in vivo retention. Moreover, ICG was introduced into the CNC/LAP gel system to induce hyperthermia of tumor tissue, amplifying the CDT effect; GOx was used for glucose deprivation (related to the Warburg effect); and Cu was introduced for hydroxyl radical generation (based on Fenton-like chemistry) and cellular glutathione (GSH) degradation in cancer cells. The ICG/GOx/Cu-installed CNC/LAP gel in combination with near-infrared (NIR) laser realized improved antiproliferation, cellular reactive oxygen species (ROS) generation, cellular GSH degradation, and apoptosis induction in colorectal cancer (CT-26) cells. In addition, local injection of the CNC/ICG/GOx/Cu/LAP gel into the implanted CT-26 tumor while irradiating it with NIR laser provided strong tumor growth suppression effects. In conclusion, the designed hybrid nanorod/nanodisk gel network can be efficiently applied to the local PTT/ST/CDT of cancer cells.
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Several microfabrication technologies have been used to engineer native-like skeletal muscle tissues. However, the successful development of muscle remains a significant challenge in the tissue engineering field. Muscle tissue engineering aims to combine muscle precursor cells aligned within a highly organized 3D structure and biological factors crucial to support cell differentiation and maturation into functional myotubes and myofibers. In this study, the use of 3D bioprinting is proposed for the fabrication of muscle tissues using gelatin methacryloyl (GelMA) incorporating sustained insulin-like growth factor-1 (IGF-1)-releasing microparticles and myoblast cells. This study hypothesizes that functional and mature myotubes will be obtained more efficiently using a bioink that can release IGF-1 sustainably for in vitro muscle engineering. Synthesized microfluidic-assisted polymeric microparticles demonstrate successful adsorption of IGF-1 and sustained release of IGF-1 at physiological pH for at least 21 days. Incorporating the IGF-1-releasing microparticles in the GelMA bioink assisted in promoting the alignment of myoblasts and differentiation into myotubes. Furthermore, the myotubes show spontaneous contraction in the muscle constructs bioprinted with IGF-1-releasing bioink. The proposed bioprinting strategy aims to improve the development of new therapies applied to the regeneration and maturation of muscle tissues.
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Bioimpresión , Andamios del Tejido , Andamios del Tejido/química , Factor I del Crecimiento Similar a la Insulina/farmacología , Ingeniería de Tejidos , Músculo Esquelético/fisiología , Fibras Musculares Esqueléticas , Hidrogeles/farmacología , Hidrogeles/química , Gelatina/farmacología , Gelatina/química , Impresión TridimensionalRESUMEN
Fused deposition modeling (FDM) is a three-dimensional (3D) printing technology typically used in tissue engineering. However, 3D-printed row scaffolds manufactured using material extrusion techniques have low cell affinity on the surface and an insufficient biocompatible environment for desirable tissue regeneration. Thus, in this study, plasma treatment was used to render surface modification for enhancing the biocompatibility of 3D-printed scaffolds. We designed a plasma-based 3D printing system with dual heads comprising a plasma device and a regular 3D FDM printer head for a layer-by-layer nitrogen plasma treatment. Accordingly, the wettability, roughness, and protein adsorption capability of the 3D-printed scaffold significantly increased with the plasma treatment time. Hence, the layer-by-layer plasma-treated (LBLT) scaffold exhibited significantly enhanced cell adhesion and proliferation in anin vitroassay. Furthermore, the LBLT scaffold demonstrated a higher tissue infiltration and lower collagen encapsulation than those demonstrated by a non-plasma-treated scaffold in anin vivoassay. Our approach has great potential for various tissue-engineering applications via the adjustment of gas or precursor levels. In particular, this system can fabricate scaffolds capable of holding a biocompatible surface on an entire 3D-printed strut. Thus, our one-step 3D printing approach is a promising platform to overcome the limitations of current biocompatible 3D scaffold engineering.
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Ingeniería de Tejidos , Andamios del Tejido , Ingeniería de Tejidos/métodos , Colágeno , Adhesión Celular , Impresión TridimensionalRESUMEN
Three-dimensional (3D)in vitrotumor models that can capture the pathophysiology of human tumors are essential for cancer biology and drug development. However, simulating the tumor microenvironment is still challenging because it consists of a heterogeneous mixture of various cellular components and biological factors. In this regard, current extracellular matrix (ECM)-mimicking hydrogels used in tumor tissue engineering lack physical interactions that can keep biological factors released by encapsulated cells within the hydrogel and improve paracrine interactions. Here, we developed a nanoengineered ion-covalent cross-linkable bioink to construct 3D bioprinted organotypic tumor models. The bioink was designed to implement the tumor ECM by creating an interpenetrating network composed of gelatin methacryloyl (GelMA), a light cross-linkable polymer, and synthetic nanosilicate (Laponite) that exhibits a unique ionic charge to improve retention of biological factors released by the encapsulated cells and assist in paracrine signals. The physical properties related to printability were evaluated to analyze the effect of Laponite hydrogel on bioink. Low GelMA (5%) with high Laponite (2.5%-3.5%) composite hydrogels and high GelMA (10%) with low Laponite (1.0%-2.0%) composite hydrogels showed acceptable mechanical properties for 3D printing. However, a low GelMA composite hydrogel with a high Laponite content could not provide acceptable cell viability. Fluorescent cell labeling studies showed that as the proportion of Laponite increased, the cells became more aggregated to form larger 3D tumor structures. Reverse transcription-polymerase chain reaction (RT-qPCR) and western blot experiments showed that an increase in the Laponite ratio induces upregulation of growth factor and tissue remodeling-related genes and proteins in tumor cells. In contrast, cell cycle and proliferation-related genes were downregulated. On the other hand, concerning fibroblasts, the increase in the Laponite ratio indicated an overall upregulation of the mesenchymal phenotype-related genes and proteins. Our study may provide a rationale for using Laponite-based hydrogels in 3D cancer modeling.
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Bioimpresión , Neoplasias , Humanos , Andamios del Tejido/química , Bioimpresión/métodos , Ingeniería de Tejidos/métodos , Gelatina/química , Impresión Tridimensional , Hidrogeles/farmacología , Hidrogeles/química , Factores Biológicos , Microambiente TumoralRESUMEN
Hemorrhage and bacterial infections are major hurdles in the management of life-threatening surgical wounds. Most bioadhesives for wound closure lack sufficient hemostatic and antibacterial properties. Furthermore, they suffer from weak sealing efficacy, particularly for stretchable organs, such as the lung and bladder. Accordingly, there is an unmet need for mechanically robust hemostatic sealants with simultaneous antibacterial effects. Here, an injectable, photocrosslinkable, and stretchable hydrogel sealant based on gelatin methacryloyl (GelMA), supplemented with antibacterial zinc ferrite (ZF) nanoparticles and hemostatic silicate nanoplatelets (SNs) for rapid blood coagulation is nanoengineered. The hydrogel reduces the in vitro viability of Staphylococcus aureus by more than 90%. The addition of SNs (2% w/v) and ZF nanoparticles (1.5 mg mL-1 ) to GelMA (20% w/v) improves the burst pressure of perforated ex vivo porcine lungs by more than 40%. Such enhancement translated to ≈250% improvement in the tissue sealing capability compared with a commercial hemostatic sealant, Evicel. Furthermore, the hydrogels reduce bleeding by ≈50% in rat bleeding models. The nanoengineered hydrogel may open new translational opportunities for the effective sealing of complex wounds that require mechanical flexibility, infection management, and hemostasis.
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Hemostáticos , Hidrogeles , Ratas , Porcinos , Animales , Hidrogeles/farmacología , Hemostáticos/farmacología , Hemostasis , Antibacterianos/farmacología , Silicatos/farmacologíaRESUMEN
Developing theranostic devices to detect bleeding and effectively control hemorrhage in the prehospital setting is an unmet medical need. Herein, an all-in-one theranostic platform is presented, which is constructed by sandwiching silk fibroin (SF) between two silver nanowire (AgNW) based conductive electrodes to non-enzymatically diagnose local bleeding and stop the hemorrhage at the wound site. Taking advantage of the hemostatic property of natural SF, the device is composed of a shape-memory SF sponge, facilitating blood clotting, with ≈82% reduction in hemostatic time in vitro as compared with untreated blood. Furthermore, this sandwiched platform serves as a capacitive sensor that can detect bleeding and differentiate between blood and other body fluids (i.e., serum and water) via capacitance change. In addition, the AgNW electrode endows anti-infection efficiency against Escherichia coli and Staphylococcus aureus. Also, the device shows excellent biocompatibility and gradually biodegrades in vivo with no major local or systemic inflammatory responses. More importantly, the theranostic platform presents considerable hemostatic efficacy comparable with a commercial hemostat, Dengen, in rat liver bleeding models. The theranostic platform provides an unexplored strategy for the intelligent management of hemorrhage, with the potential to significantly improve patients' well-being through the integration of diagnostic and therapeutic capabilities.
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Fibroínas , Hemostáticos , Nanocables , Ratas , Animales , Medicina de Precisión , Plata/uso terapéutico , Hemorragia/tratamiento farmacológico , Hemostáticos/uso terapéutico , Hemostáticos/metabolismoRESUMEN
Aerogel-based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol-gel, aging, drying, and self-assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic-based technologies and 3D printing can be combined with aerogel-based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel-based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels.
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Materiales Biocompatibles , Ingeniería de Tejidos , Desecación/métodos , Cicatrización de HeridasRESUMEN
Peptide-based hydrogel biomaterials have emerged as an excellent strategy for immune system modulation. Peptide-based hydrogels are supramolecular materials that self-assemble into various nanostructures through various interactive forces (i.e., hydrogen bonding and hydrophobic interactions) and respond to microenvironmental stimuli (i.e., pH, temperature). While they have been reported in numerous biomedical applications, they have recently been deemed promising candidates to improve the efficacy of cancer immunotherapies and treatments. Immunotherapies seek to harness the body's immune system to preemptively protect against and treat various diseases, such as cancer. However, their low efficacy rates result in limited patient responses to treatment. Here, the immunomaterial's potential to improve these efficacy rates by either functioning as immune stimulators through direct immune system interactions and/or delivering a range of immune agents is highlighted. The chemical and physical properties of these peptide-based materials that lead to immuno modulation and how one may design a system to achieve desired immune responses in a controllable manner are discussed. Works in the literature that reports peptide hydrogels as adjuvant systems and for the delivery of immunotherapies are highlighted. Finally, the future trends and possible developments based on peptide hydrogels for cancer immunotherapy applications are discussed.
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Nanoestructuras , Neoplasias , Humanos , Hidrogeles/química , Inmunoterapia , Péptidos/química , Nanoestructuras/química , Neoplasias/terapiaRESUMEN
The tumor microenvironment consists of diverse, complex etiological factors. The matrix component of pancreatic ductal adenocarcinoma (PDAC) plays an important role not only in physical properties such as tissue rigidity but also in cancer progression and therapeutic responsiveness. Although significant efforts have been made to model desmoplastic PDAC, existing models could not fully recapitulate the etiology to mimic and understand the progression of PDAC. Here, two major components in desmoplastic pancreatic matrices, hyaluronic acid- and gelatin-based hydrogels, are engineered to provide matrices for tumor spheroids composed of PDAC and cancer-associated fibroblasts (CAF). Shape analysis profiles reveals that incorporating CAF contributes to a more compact tissue formation. Higher expression levels of markers associated with proliferation, epithelial to mesenchymal transition, mechanotransduction, and progression are observed for cancer-CAF spheroids cultured in hyper desmoplastic matrix-mimicking hydrogels, while the trend can be observed when those are cultured in desmoplastic matrix-mimicking hydrogels with the presence of transforming growth factor-ß1 (TGF-ß1). The proposed multicellular pancreatic tumor model, in combination with proper mechanical properties and TGF-ß1 supplement, makes strides in developing advanced pancreatic models for resembling and monitoring the progression of pancreatic tumors, which could be potentially applicable for realizing personalized medicine and drug testing applications.
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This study analyzed the relationship between the lunar phase and the reproductive cycle of Pinctada margaritifera inhabiting Weno Island, Chuuk Lagoon, Micronesia. We measured indicators of maturity (gonadosomatic index [GSI] and sexual maturation-related genes) and investigated changes in the gonadal maturity stages (GMS) of P. margaritifera over lunar cycle. GSI was higher around the full moon. GMS of P. margaritifera were classified as the early gametogenesis stage, ripe and spawning stage, and spent and degenerating stage. A large percentage of oysters was observed in the ripe and spawning stage at the first quarter moon in female and the full moon in male as well as in the spent and degenerating stages at the third quarter moon in both sexes. In addition, the expression of doublesex- and mab-3-related transcription factor 2 (DMRT2) in the male P. margaritifera black-lip pearl oyster was the highest during the full and third quarter moon phases, whereas no difference in expression was observed with the lunar phase in females. In contrast, the expression of vitellogenin (VTG) was the highest in female P. margaritifera during the first and third quarters. No difference in expression was observed according to the lunar phase in males. The results suggest that the lunar phase directly affects the expression of sexually mature gonads in P. margaritifera black-lip pearl oyster.
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Pinctada , Femenino , Masculino , Animales , Pinctada/genética , Luna , Gónadas , Reproducción , Maduración SexualRESUMEN
The remarkable ability of biological systems to sense and adapt to complex environmental conditions has inspired new materials and novel designs for next-generation wearable devices. Hydrogels are being intensively investigated for their versatile functions in wearable devices due to their superior softness, biocompatibility, and rapid stimulus response. This review focuses on recent strategies for developing bioinspired hydrogel wearable devices that can accommodate mechanical strain and integrate seamlessly with biological systems. We will provide an overview of different types of bioinspired hydrogels tailored for wearable devices. Next, we will discuss the recent progress of bioinspired hydrogel wearable devices such as electronic skin and smart contact lenses. Also, we will comprehensively summarize biosignal readout methods for hydrogel wearable devices as well as advances in powering and wireless data transmission technologies. Finally, current challenges facing these wearable devices are discussed, and future directions are proposed.
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Materiales Biomiméticos , Dispositivos Electrónicos Vestibles , HidrogelesRESUMEN
Shear-thinning biomaterials (STBs) based on gelatin-silicate nanoplatelets (SNs) are emerging as an alternative to conventional coiling and clipping techniques in the treatment of vascular anomalies. Improvements in the cohesion of STB hydrogels pave the way toward their translational application in minimally invasive therapies such as endovascular embolization repair. In the present study, sodium phytate (Phyt) additives are used to tune the electrostatic network of SNs-gelatin STBs, thereby promoting their mechanical integrity and facilitating injectability through standard catheters. We show that an optimized amount of Phyt enhances storage modulus by approximately one order of magnitude and reduces injection force by ≈58% without compromising biocompatibility and hydrogel wet stability. The Phyt additives are found to decrease the immune responses induced by SNs. In vitro embolization experiments suggest a significantly lower rate of failure in Phyt-incorporated STBs than in control groups. Furthermore, the addition of Phyt leads to accelerated blood coagulation (reduces clotting time by ≈45% compared to controls) due to the contributions of negatively charged phosphate groups, which aid in the prolonged durability of STB in coagulopathic patients. Therefore, the proposed approach is an effective method for the design of robust and injectable STBs for minimally invasive treatment of vascular malformations.
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Materiales Biocompatibles , Hemostáticos , Humanos , Materiales Biocompatibles/farmacología , Gelatina/farmacología , Ácido Fítico , Silicatos/farmacología , Hidrogeles/farmacologíaRESUMEN
Blood loss by hemorrhaging wounds accounts for over one-third of â¼5 million trauma fatalities worldwide every year. If not controlled in a timely manner, exsanguination can take lives within a few minutes. Developing new biomaterials that are easy to use by non-expert patients and promote rapid blood coagulation is an unmet medical need. Here, biocompatible, and biodegradable microneedle arrays (MNAs) based on gelatin methacryloyl (GelMA) biomaterial hybridized with silicate nanoplatelets (SNs) are developed for hemorrhage control. The SNs render the MNAs hemostatic, while the needle-shaped structure increases the contact area with blood, synergistically accelerating the clotting time from 11.5â¯min to 1.3â¯min in vitro. The engineered MNAs reduce bleeding by â¼92% compared with the untreated injury group in a rat liver bleeding model. SN-containing MNAs outperform the hemostatic effect of needle-free patches and a commercial hemostat in vivo via combining micro- and nanoengineered features. Furthermore, the tissue adhesive properties and mechanical interlocking support the suitability of MNAs for wound closure applications. These hemostatic MNAs may enable rapid hemorrhage control, particularly for patients in developing countries or remote areas with limited or no immediate access to hospitals.
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Sac embolization of abdominal aortic aneurysms (AAAs) remains clinically limited by endoleak recurrences. These recurrences are correlated with recanalization due to the presence of endothelial lining and matrix metalloproteinases (MMPs)-mediated aneurysm progression. This study incorporated doxycycline (DOX), a well-known sclerosant and MMPs inhibitor, into a shear-thinning biomaterial (STB)-based vascular embolizing hydrogel. The addition of DOX was expected to improve embolizing efficacy while preventing endoleaks by inhibiting MMP activity and promoting endothelial removal. The results showed that STBs containing 4.5% w/w silicate nanoplatelet and 0.3% w/v of DOX were injectable and had a 2-fold increase in storage modulus compared to those without DOX. STB-DOX hydrogels also reduced clotting time by 33% compared to untreated blood. The burst release of DOX from the hydrogels showed sclerosing effects after 6 h in an ex vivo pig aorta model. Sustained release of DOX from hydrogels on endothelial cells showed MMP inhibition (ca. an order of magnitude larger than control groups) after 7 days. The hydrogels successfully occluded a patient-derived abdominal aneurysm model at physiological blood pressures and flow rates. The sclerosing and MMP inhibition characteristics in the engineered multifunctional STB-DOX hydrogels may provide promising opportunities for the efficient embolization of aneurysms in blood vessels.